Antimalarial and β-hematin formation inhibitory activities of chromone derivatives

A series of chromone compounds were evaluated as new potential antimalarial agents using in vitro antimalarial activity assay. The most potent compound 36 with an IC50 of 0.95 mu M was shown to be more potent than primaquine and tafenoquine (IC50 2.41 and 1.95 mu M, respectively). beta-Hematin formation inhibitory activity test and stoichiometry determination have also been performed to investigate the preliminary mechanism of antimalarial activity of the studied compounds. Compounds 23-28 (IC50 1.41, 1.76, 2.30, 2.54, 4.60, and 3.69 mu M, respectively) displayed greater beta-hematin formation inhibitory activity than chloroquine, dihydroartemisinin, and mefloquine (IC50 25.04, 18.04, 15.78 mu M, respectively). Compounds 3, 4, 23, 24, 27, 36, 38, and 43 showed high potency in both antimalarial and beta-hematin formation assays. Job's plots indicated that compounds showing high beta-hematin formation inhibitory activity formed stable complexes with the same stoichiometric ratio of chromone:heme = 1:2 as chloroquine. This study opens up the possibility of development of chromone derivatives as new antimalarials targeting beta-hematin formation.